Patent GB-955692-A (GB)
Title: Improvements in or relating to a process for the preparation of steroidal lactones
IPC: C07J75/00
Filed: 1960-10-25
Abstract: The invention comprises a process for the preparation of steroidal 11-hydroxy-18-oic acid 11, 18-lactones by oxidizing 11, 18-epoxy-steroids with ozone or ruthenium tetroxide, and 11, 18-lactones of the general formula: <FORM:0955692/C2/1> wherein R1 represents a hydrogen or fluorine atom, R2 represents a hydrogen or fluorine atom or a methyl group, R3 and R4 represent a hydrogen atom or a methyl group, and Ac is a lower alkanoyl group containing 2 to 7 carbon atoms which may be prepared by the above process. In the above process other non-reactive substituents such as halogen, alkyl, keto or alkanoyloxy substituents may be present in various positions of the steroid nuclear.  Conanines of the general formula: <FORM:0955692/C2/2> wherein R1, R2, R3 and R4 have the above significance, and R5 represents a hydroxy, acetoxy or keto group, are prepared by reacting the required 20-keto-steroid compounds with a primary lower alkylamine under mild hydrogenation conditions, treating the resulting 20-monoalkylamino-steroid compounds with a halogenating agent, such as N-chlorosuccinimide, to form 20-N-haloamino-steroid compounds, and irradiating this compound with ultra-violet light in the presence of trifluoroacetic acid.  An 11-keto group in the final product may be reduced to an 11b -hydroxy group, e.g. with lithium aluminium hydride.  Steroids of the general formula: <FORM:0955692/C2/3> wherein R1 to R4 and Ac have the above significance, are prepared by converting the conanines of the general formula in the previous paragraph into quaternary salts, preferably by reaction with an alkyl halide, converting the quaternary salts into the corresponding quaternary ammonium hydroxides, heating the quaternary ammonium hydroxides to form D 20-steroids of the general formula: <FORM:0955692/C2/4> wherein R1 to R5 have the above significance and X is the hydroxide anion, treating these compounds with a strong base to convert the 11b -hydroxyl group into an 11-alkoxide anion and heating and, if necessary oxidizing a 3-hydroxy group to a 3-keto group, to form steroids of the general formula: <FORM:0955692/C2/5> wherein R1 to R4 have the above significance, oxygenating these compounds at the 20, 21-positions, for example, with osmium tetroxide with or without organic iodoso compounds, potassium permanganate in pyridine, or osmium tetroxide-potassium perchlorate, and when required decomposing the resulting osmate esters, for example, with ethanolic sodium sulphite, to form the 20, 21-diols of the general formula: <FORM:0955692/C2/6> wherein R1 to R4 have the above significance and acylating the 20, 21-diols as required.  3b -Acetoxy-9a -fluoro-allopregnan-11, 20-dione is prepared by treating 3b -acetoxy-9(11)-allopregnen-20-one with N-bromoacetamide and perchloric acid to form 3b -acetoxy-9b , 11b -epoxy-allopregnan-20-one, treating this compound with hydrogen fluoride and oxidizing the resulting 3b -acetoxy-9a -fluoro-allopregnan-11b -ol-20-one.  19 - Norallopregnane - 3b , 11b - diol -20- one 3-acetate is prepared by hydrogenating 19-nor-4-pregnene-3b , 11b -diol-20-one to form 19-norallopregnane-3b , 11b -diol-20-one and treating this compound with one mole of acetic anhydride.  3b -Acetoxy-6b , 9a -difluoro-allopregnane-11,20-dione is prepared by hydrogenating 6b , 9a -difluoro-4-pregnene-3, 11, 20-trione to form 6b , 9a -difluoro-allopregnane-3, 11, 20-trione, reducing this compound with sodium borohydride and acetylating the resulting 3b -hydroxy-6b , 9a -difluoro-allopregnane-11, 20-dione. Specifications 933,154, 933,155, 933,156, 933,157 and 948,268 are referred to.